Why is the dog an ideal model for aging research?

Gilmore, Keiva M.; Greer, Kimberly A.

doi:10.1016/j.exger.2015.08.008

Cited by 68 publications

(65 citation statements)

References 89 publications

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“…The rapidity with which dogs age, relative to people, is a major strength when it comes to investigating the biological mechanisms of aging, because age-related changes can be assessed over a much shorter period of time (Gilmore and Greer 2015). This is true both for longitudinal studies of aging, where animals are followed throughout life, as well as for clinical trials to assess the efficacy of interventions on healthy aging and disease burden (both are discussed further below).…”

Section: Making the Case For Canine Gerosciencementioning

confidence: 99%

The dog aging project: translational geroscience in companion animals

2016

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Studies of the basic biology of aging have identified several genetic and pharmacological interventions that appear to modulate the rate of aging in laboratory model organisms, but a barrier to further progress has been the challenge of moving beyond these laboratory discoveries to impact health and quality of life for people. The domestic dog, Canis familiaris, offers a unique opportunity for surmounting this barrier in the near future. In particular, companion dogs share our environment and play an important role in improving the quality of life for millions of people. Here we present a rationale for increasing the role of companion dogs as an animal model for both basic and clinical Geroscience and describe complementary approaches and ongoing projects aimed at achieving this goal.

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Section: Making the Case For Canine Gerosciencementioning

confidence: 99%

The dog aging project: translational geroscience in companion animals

2016

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“…Compared to the commonly used model organisms, companion dogs (Canis lupus familiaris) have great translational potential for geroscience because they uniquely recapitulate many aspects of human aging, including sharing our environment, receiving comparable medical care, and often having detailed medical records available (Pitt and Kaeberlein 2015;Neff and Rine 2006;Gilmore and Greer 2015;Kaeberlein 2015). In this context, the Dog Aging Project seeks to carry out both longitudinal and interventional studies of aging in the privately owned domestic dog, both to gain new insights into mechanisms of human aging and to enhance healthspan and lifespan in dogs (Kaeberlein et al 2016;Kaeberlein 2015).…”

Section: Introductionmentioning

confidence: 99%

A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs

et al. 2017

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Age is the single greatest risk factor for most causes of morbidity and mortality in humans and their companion animals. As opposed to other model organisms used to study aging, dogs share the human environment, are subject to similar risk factors, receive comparable medical care, and develop many of the same age-related diseases humans do. In this study, 24 middle-aged healthy dogs received either placebo or a non-immunosuppressive dose of rapamycin for 10 weeks. All dogs received clinical and hematological exams before, during, and after the trial and echocardiography before and after the trial. Our results showed no clinical side effects in the rapamycin-treated group compared to dogs receiving the placebo. Echocardiography suggested improvement in both diastolic and systolic age-related measures of heart function (E/A ratio, fractional shortening, and ejection fraction) in the rapamycin-treated dogs. Hematological values remained within the normal range for all parameters studied; however, the mean corpuscular volume (MCV) was decreased in rapamycin-treated dogs. Based on these results, we will test rapamycin on a larger dog cohort for a longer period of time in order to validate its effects on cardiac function and to determine whether it can significantly improve healthspan and reduce mortality in companion dogs.

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“…Domestic dogs provide a unique opportunity to investigate the above questions (Kaeberlein, Creevy, and Promislow 2016;Gilmore and Greer 2015) . Dogs have been selectively bred by humans for occupation and aesthetics (Ostrander et al 2017) , resulting in over 450 distinct whose members share morphologic and behavior traits.…”

Section: Introductionmentioning

confidence: 99%

“…Although humans and dogs diverged early during mammalian evolution (Vonholdt et al 2010) , dogs share nearly all aspects of their environments with humans. These include, critically for these studies, similar levels of health observation and health care intervention (Kaeberlein, Creevy, and Promislow 2016;Gilmore and Greer 2015) . While average lifespan differs dramatically across breeds, within some breeds such as the Labrador retriever there are extensive variations in lifespan.…”

Section: Introductionmentioning

confidence: 99%

Quantitative translation of dog-to-human aging by conserved remodeling of epigenetic networks

Wang

Hogan

et al. 2019

Preprint

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Mammals progress through similar physiological stages during life, from early development to puberty, aging, and death. Yet, the extent to which this conserved physiology reflects conserved molecular events is unclear. Here, we map common epigenetic changes experienced by mammalian genomes as they age, focusing on evolutionary comparisons of humans to dogs, an emerging model of aging. Using targeted sequencing, we characterize the methylomes of 104Labrador retrievers spanning a 16 year age range, achieving >150X coverage within mammalian syntenic blocks. Comparison with human methylomes reveals a nonlinear relationship which translates dog to human years, aligns the timing of major physiological milestones between the two species, and extends to mice. Conserved changes center on specific developmental gene networks which are sufficient to capture the effects of anti-aging interventions in multiple mammals. These results establish methylation not only as a diagnostic age readout but as a cross-species translator of physiological aging milestones.

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Why is the dog an ideal model for aging research?

Cited by 68 publications

References 89 publications

The dog aging project: translational geroscience in companion animals

The dog aging project: translational geroscience in companion animals

A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs

Quantitative translation of dog-to-human aging by conserved remodeling of epigenetic networks

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